tbuckley/cabot-search huggingface dataset:
SGLT2-inhibitors reduce the cardiac autonomic neuropathy dysfunction and vaso-vagal syncope recurrence in patients with type 2 diabetes mellitus: the SCAN study
Authors: Celestino Sardu, M Massimo Massetti, Pietro Rambaldi, Gianluca Gatta, Salvatore Cappabianca, Ferdinando Carlo Sasso, Matteo Santamaria, Mario Volpicelli, Valentino Ducceschi, Giuseppe Signoriello, Giuseppe Paolisso, Raffaele Marfella
Journal: Metabolism (2022)

In patients with type 2 diabetes mellitus (T2DM) the vaso-vagal syncope (VVS) recurrence could be due to the alteration of autonomic system function, evaluated by heart rate variability (HRV), and by 123I-metaiodobenzylguanidine (123I-mIBG) myocardial scintigraphy indexes: Heart to Mediastinum ratio (H/Mlate), and Washout rate (WR). The SGLT2-I could modulate/reduce autonomic dysfunction in T2DM patients with VVS. This effect could reduce the VVS recurrence in T2DM patients.In a prospective multicenter study, after propensity score matching, we studied a population of 324 T2DM patients with VVS, divided into 161 SGLT2-I-users vs. 163 Non-SGLT2-I users. In these patients as SGLT2-I-users vs. Non-SGLT2-I users, we investigated the HRV and 123I-MIBG modifications and VVS recurrence at 12 months of follow-up.At follow-up end, the SGLT2-I-users vs. Non-SGLT2-I users had best glucose homeostasis and lower values of inflammatory markers, and resting heart rate (p < 0.05). The SGLT2-I-users vs. Non-SGLT2-I users evidenced the lowest low frequency/high frequency ratio (LF/HFr), a significant difference for all the indexes of autonomic dysfunction via ECG Holter analysis, and higher values of H/Mlate (p < 0.05). Finally, comparing SGLT2-I-users vs. Non-SGLT2-I users, we found a higher rate of VVS recurrence events, specifically of the vasodepressor VVS recurrence at 1-year follow-up (p < 0.05). We did not find a significant difference of mixed and cardio-inhibitory VVS recurrence events at 1 year of follow-up in the study cohorts (p > 0.05). At the Cox regression analysis H/Mlate (0.710, [0.481-0.985]), and SGLT2-I therapy (0.550, [0.324-0.934]) predicted all causes of syncope recurrence at 1 year of follow-up.Non-SGLT2-I users vs. SGLT2-I-users had alterations of the autonomic nervous system, with a higher rate of VVS recurrence at 1 year of follow-up. The indexes of cardiac denervation predicted the VVS recurrence, while the SGLT2-I reduced the risk of VVS recurrence.NCT03717207.
SeqScreen: accurate and sensitive functional screening of pathogenic sequences via ensemble learning
Authors: Advait Balaji, Bryce Kille, Anthony D. Kappell, Gene D. Godbold, Madeline Diep, R. A. Leo Elworth, Zhiqin Qian, Dreycey Albin, Daniel J. Nasko, Nidhi Shah, Mihai Pop, Santiago Segarra, Krista L. Ternus, Todd J. Treangen
Journal: Genome biology (2022)

Abstract The COVID-19 pandemic has emphasized the importance of accurate detection of known and emerging pathogens. However, robust characterization of pathogenic sequences remains an open challenge. To address this need we developed SeqScreen, which accurately characterizes short nucleotide sequences using taxonomic and functional labels and a customized set of curated Functions of Sequences of Concern (FunSoCs) specific to microbial pathogenesis. We show our ensemble machine learning model can label protein-coding sequences with FunSoCs with high recall and precision. SeqScreen is a step towards a novel paradigm of functionally informed synthetic DNA screening and pathogen characterization, available for download at www.gitlab.com/treangenlab/seqscreen .
Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant
Authors: Kirsten E. Lyke, Robert L. Atmar, Clara Dominguez Islas, Christine M. Posavad, Daniel Szydlo, Rahul Paul Chourdhury, Meagan E. Deming, Amanda Eaton, Lisa A. Jackson, Angela R. Branche, Hana M. El Sahly, Christina A. Rostad, Judith M. Martin, Christine Johnston, Richard E. Rupp, Mark J. Mulligan, Rebecca C. Brady, Robert W. Frenck, Martín Bäcker, Angelica C. Kottkamp, Tara M. Babu, Kumaravel Rajakumar, Srilatha Edupuganti, David Dobrzynski, Rhea N. Coler, Janet I. Archer, Sonja Crandon, Jillian A. Zemanek, Elizabeth R. Brown, Kathleen M. Neuzil, David S. Stephens, Diane J. Post, Seema U. Nayak, Mehul S. Suthar, Paul C. Roberts, John H. Beigel, David C. Montefiori, Jennifer S. Husson, Angie Price, Jennifer A. Whitaker, Wendy A. Keitel, Ann R. Falsey, Ian Shannon, Daniel Graciaa, Nadine Rouphael, Evan J. Anderson, Satoshi Kamidani, Gysella B. Muniz, Sonika Bhatnagar, Anna Wald, Megan Berman, Laura Porterfield, Amber Stanford, Jennifer Lee Dong, Steven E. Carsons, Diana Badillo, Susan Parker, Michelle Dickey, Sasha E. Larsen, John Hural, Brian Ingersoll, Marina Lee, Lilin Lai, Katharine Floyd, Madison Ellis, Kathryn M. Moore, Kelly Manning, Stephanie L. Foster, Mit Patel
Journal: Cell Reports Medicine (2022)

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.
Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia
Authors: Javier Garcia-Bermudez, Michael A. Badgley, Sheela Prasad, Lou Baudrier, Yuyang Liu, Konnor La, Mariluz Soula, Robert T. Williams, Norihiro Yamaguchi, Rosa F. Hwang, Laura J. Taylor, Elisa de Stanchina, Bety Rostandy, Hanan Alwaseem, Henrik Molina, Dafna Bar-Sagi, Kıvanç Birsoy
Journal: Nature Metabolism (2022)
Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target
Authors: Giorgia Alvisi, Alberto Termanini, Cristiana Soldani, Federica Portale, Roberta Carriero, Karolina Pilipow, Guido Costa, Michela Polidoro, Barbara Franceschini, Ines Malenica, Simone Puccio, Veronica Lise, Giovanni Galletti, Veronica Zanon, Federico Simone Colombo, Gabriele De Simone, Michele Tufano, Alessio Aghemo, Luca Di Tommaso, Clelia Peano, Javier Cibella, Matteo Iannacone, Rahul Roychoudhuri, Teresa Manzo, Matteo Donadon, Guido Torzilli, Paolo Kunderfranco, Diletta Di Mitri, Enrico Lugli, Ana Lleo
Journal: Journal of Hepatology (2022)
Abstract 6369: Discovery of potent, orally bioavailable, brain penetrant RAD51 inhibitor as an anti-cancer agent
Authors: Sanjita Sasmal, Sukanya Patra, Venkatesham Boorgu, Shankar Chithaluri, Mahesh Yanamadra, Deepika Hiremath, Hemashankar Pathange, Sandeep M. Girme, Amitkumar Pawar, Rutuja Narayan Shinde, Nilanjan Samanta
Journal: Cancer Research (2022)

Abstract Proliferating cells undergo DNA damage, and this is more pronounced in cancer cells due to their high rate of proliferation. Cancer cells are thus more dependent on the DNA damage repair pathway for their survival. Double-strand breaks (DSBs) are amongst the most severe type of DNA damage and are predominantly repaired by homologous recombination (HR) in an error-free manner. RAD51 is a pivotal recombinase for DSB repair by the HR pathway. Binding of RAD51 with BRCA2 followed by its nuclear translocation, is one of the key repair mechanisms for RAD51 mediated DSB repair. We have identified novel and potent RAD51 inhibitors disrupting the RAD51:BRCA2 interaction, which can address BRCA2 WT patient population. Upon induction of exogenous DNA damage, our compounds inhibit nuclear RAD51 foci formation and demonstrate sustained γH2AX accumulation in the nucleus, suggesting persistent DNA damage. Our orally bioavailable &amp; brain penetrant lead compound shows anti-proliferative activity in multiple BRCA2 WT cancer cell lines across various indications, and excellent synergy when combined with PARP1 inhibitors such as Olaparib. Further, in a wound healing assay, treatment with our lead compound inhibits cell migration in a dose-dependent manner. TNBC patients with extensive brain metastasis have limited treatment options. Thus, a brain penetrant RAD51 inhibitor could provide a novel treatment option in this setting. Citation Format: Sanjita Sasmal, Sukanya Patra, Venkatesham Boorgu, Shankar Chithaluri, Mahesh Yanamadra, Deepika Hiremath, Hemashankar Pathange, Sandeep M. Girme, Amitkumar Pawar, Rutuja Narayan Shinde, Nilanjan Samanta. Discovery of potent, orally bioavailable, brain penetrant RAD51 inhibitor as an anti-cancer agent [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6369.
Errors in Byline and Figure 2
Authors: John Mcdermott, William Newman
Journal: JAMA Pediatrics (2022)

Nader Shaikh, MD, MPH; Matthew C. Lee, BA; Lynissa R. Stokes, PhD; Elizabeth Miller, MD, PhD; Marcia Kurs-Lasky, MS; Isabella Conway, BS; Timothy R. Shope, MD; Alejandro Hoberman, MD
Correction to: Comparison of 8 versus 15 days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial
Authors: Adrien Bouglé, Sophie Tuffet, Laura Federici, Marc Leone, Antoine Monsel, Thomas Dessalle, Julien Amour, Claire Dahyot-Fizelier, François Barbier, Charles-Edouard Luyt, Olivier Langeron, Bernard Cholley, Julien Pottecher, Tarik Hissem, Jean-Yves Lefrant, Benoit Veber, Matthieu Legrand, Alexandre Demoule, Pierre Kalfon, Jean-Michel Constantin, Alexandra Rousseau, Tabassome Simon, Arnaud Foucrier, Adrien Bouglé, Julien Amour, Thomas Dessalle, Florence Bellenfant Zegdi, Bernard Cholley, Julien Massot, Jean-Michel Constantin, Alexandre Demoule, Julien Mayaux, Vincent Dubée, Hervé Dupont, Jacques Duranteau, Laura Federici, Arnaud Foucrier, Thomas Geeraerts, Céline Guichon, Pierre Kalfon, Éric Kipnis, Sigismond Lasocki, Jean-Yves Lefrant, Matthieu Legrand, Marc Leone, Thomas Lescot, Bruno Lévy, Joël Cousson, Philippe Montravers, Sébastien Tanaka, Emmanuel Novy, Alexandre Ouattara, Jean-François Payen, Walter Picard, Pascale Poète, Julien Pottecher, Christophe Quesnel, Muriel Fartoukh, Anoine Tesniere, Mélanie Fromentin, Jean-Jacques Rouby, Qin Lu, Olivier Langeron, Pierre Squara, Eric Levesque, Nicolas Mongardon, Tabassome Simon, Laurence Berard, Marine Cachanado, Nora Soussi
Journal: Intensive Care Medicine (2022)
Lipid-peptide nanocomplexes for mRNA delivery in vitro and in vivo
Authors: Dania Grant-Serroukh, Morag R. Hunter, Ruhina Maeshima, Aristides D. Tagalakis, Ahmad M. Aldossary, Nour Allahham, Gareth R. Williams, Mark Edbrooke, Arpan Desai, Stephen L. Hart
Journal: Journal of Controlled Release (2022)

Despite recent advances in the field of mRNA therapy, the lack of safe and efficacious delivery vehicles with pharmaceutically developable properties remains a major limitation. Here, we describe the systematic optimisation of lipid-peptide nanocomplexes for the delivery of mRNA in two murine cancer cell types, B16-F10 melanoma and CT26 colon carcinoma as well as NCI-H358 human lung bronchoalveolar cells. Different combinations of lipids and peptides were screened from an original lipid-peptide nanocomplex formulation for improved luciferase mRNA transfection in vitro by a multi-factorial screening approach. This led to the identification of key structural elements within the nanocomplex associated with substantial improvements in mRNA transfection efficiency included alkyl tail length of the cationic lipid, the fusogenic phospholipid, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and cholesterol. The peptide component (K16GACYGLPHKFCG) was further improved by the inclusion of a linker, RVRR, that is cleavable by the endosomal enzymes cathepsin B and furin, and a hydrophobic motif (X-S-X) between the mRNA packaging (K16) and receptor targeting domains (CYGLPHKFCG). Nanocomplex transfections of a murine B16-F10 melanoma tumour supported the inclusion of cholesterol for optimal transfection in vivo as well as in vitro. In vitro transfections were also performed with mRNA encoding interleukin-15 as a potential immunotherapy agent and again, the optimised formulation with the key structural elements demonstrated significantly higher expression than the original formulation. Physicochemical characterisation of the nanocomplexes over time indicated that the optimal formulation retained biophysical properties such as size, charge and mRNA complexation efficiency for 14 days upon storage at 4 °C without the need for additional stabilising agents. In summary, we have developed an efficacious lipid-peptide nanocomplex with promising pharmaceutical development properties for the delivery of therapeutic mRNA.
Art v 1 IgE epitopes of patients and humanized mice are conformational
Authors: Maja Zabel, Milena Weber, Bernhard Kratzer, Cordula Köhler, Beatrice Jahn-Schmid, Gabriele Gadermaier, Pia Gattinger, Urška Bidovec-Stojkovič, Peter Korošec, Ursula Smole, Gert Wurzinger, Kuan-Wei Chen, Carmen Bunu Panaitescu, Ludger Klimek, Isabel Pablos, Katarzyna Niespodziana, Alina Neunkirchner, Walter Keller, Rudolf Valenta, Winfried F Pickl
Journal: Journal of Allergy and Clinical Immunology (2022)
Dental plaque-inspired versatile nanosystem for caries prevention and tooth restoration
Authors: Yue Xu, Yuan You, Luyao Yi, Xiaoyi Wu, Yaning Zhao, Jian Yu, He Liu, Ya Shen, Jingmei Guo, Cui Huang
Journal: Bioactive Materials (2022)

Dental caries is one of the most prevalent human diseases resulting from tooth demineralization caused by acid production of bacteria plaque. It remains challenges for current practice to specifically identify, intervene and interrupt the development of caries while restoring defects. In this study, inspired by natural dental plaque, a stimuli-responsive multidrug delivery system (PMs@NaF-SAP) has been developed to prevent tooth decay and promote enamel restoration. Classic spherical core-shell structures of micelles dual-loaded with antibacterial and restorative agents are self-assembled into bacteria-responsive multidrug delivery system based on the pH-cleavable boronate ester bond, followed by conjugation with salivary-acquired peptide (SAP) to endow the nanoparticle with strong adhesion to tooth enamel. The constructed PMs@NaF-SAP specifically adheres to tooth, identifies cariogenic conditions and intelligently releases drugs at acidic pH, thereby providing antibacterial adhesion and cariogenic biofilm resistance, and restoring the microarchitecture and mechanical properties of demineralized teeth. Topical treatment with PMs@NaF-SAP effectively diminishes the onset and severity of caries without impacting oral microbiota diversity or surrounding mucosal tissues. These findings demonstrate this novel nanotherapy has potential as a promising biomedical application for caries prevention and tooth defect restoration while resisting biofilm-associated diseases in a controlled manner activated by pathological bacteria.
Assessment of Ethnic Inequities and Subpopulation Estimates in COVID-19 Vaccination in New Zealand
Authors: Andrew Anglemyer, Corina Grey, Collin Tukuitonga, Andrew Sporle, Gerard J. B. Sonder
Journal: JAMA Network Open (2022)

This cross-sectional study investigates the outcomes of different population estimate methodologies on relative gaps in COVID-19 vaccination between ethnic groups and the resulting population risk among people in New Zealand.
Structural and functional analyses of antibodies specific for modified core N‐glycans suggest a role in <scp>T<sub>H</sub>2</scp> responses
Authors: Melanie Plum, Luna Tjerrild, Tim Raiber, Frank Bantleon, Sara Bantleon, Michaela Miehe, Frederic Jabs, Henning Seismann, Christian Möbs, Wolfgang Pfützner, Thilo Jakob, Gregers R. Andersen, Edzard Spillner
Journal: Allergy (2022)

Immune responses to N-glycan structures from allergens and parasites are often associated with pronounced, high affinity IgE reactivities. Cross-reactive carbohydrate determinants (CCDs) are constituted by modified N-glycan core structures and represent the most frequently recognized epitopes in allergic immune responses. Although recently accepted as potentially allergenic epitopes, the biological and clinical relevance as well as structural and functional characteristics of CCD-specific antibodies remain elusive.In order to gain structural insights into the recognition of CCDs, two specific antibody fragments were isolated from a leporid immune repertoire library and converted into human/leporid IgE and IgG formats. The antibody formats were assessed by ELISA and surface plasmon resonance, structural and functional analyses were performed by X-ray crystallography, mediator release, and ELIFAB assays.The recombinant IgE exhibited highly specific interactions with different types of CCDs on numerous CCD-carrying glycoproteins. Crystal structures of two CCD-specific antibodies, one of which in complex with a CCD-derived disaccharide emphasize that mechanisms of core glycan epitope recognition are as specific as those governing protein epitope recognition. The rIgE triggered immediate cellular responses via FcεRI cross-linking and mediated facilitated antigen presentation by binding of IgE/antigen complexes to CD23, a process that also could be blocked by IgG of allergic patients.Our study provides evidence for the relevance of N-glycan recognition in TH 2 responses and corroborates that IgE and IgG antibodies to ubiquitous carbohydrate epitopes can be equivalent to those directed against proteinaceous epitopes with implications for diagnostic and immunotherapeutic concepts.
Impact of Covıd-19 Pandemıc on Severe Ventrıcular Arrhythmıa and Icd Therapy
Authors: Mujdat Aktas, Abdulcebbar Sipal, Tayyar Akbulut, Faysal Saylik
Journal: Clinical Cardiology and Cardiovascular Interventions (2022)

BACKGROUND AND OBJECTIVES: The regular clinical follow-up of the patient with the implantable cardioverter-defibrillator (ICD) device was seriously affected by the COVID-19 outbreak. Due to the high risk of contamination, patients didn’t admit to the clinics for the ICD device control. It has been observed that arrhythmic events increased during the COVID-19 outbreak. In this study, we aimed to investigate the frequency of severe ventricular arrhythmias and ICD device therapy in COVID-19 patients with ICD. METHODS: In this single center-observational study, we assessed severe ventricular arrhythmias and ICD therapies by analyzing recorded data of 33 patients (24 males, 72.7%) 3 months before and after getting COVID-19 during the COVID-19 pandemic in Van, Turkey, between 15 August 2020 and 15 January 2021. RESULTS: Before the diagnosis of COVID-19, 6 ventricular tachycardias and 1 ventricular fibrillation episode were observed. When we analyzed the records after the diagnosis COVID-19, 17 ventricular tachycardia, and 3 ventricular fibrillation episodes were observed. Considering the ICD device therapies, 5 of these severe tachyarrhythmias were terminated by anti-tachycardia pacing (ATP) and 2 with shock therapy before the diagnosis of COVID-19. After the COVID-19, 14 of them were terminated by ATP, and 6 of them were terminated by shock therapy. CONCLUSION: The effects of the COVID-19 pandemic, especially on ventricular arrhythmia, have not been reported sufficiently. In our study, it was observed that life-threatening ventricular arrhythmias and the ICD therapies were increased in patients with COVID-19, especially in the first month after the diagnosis of COVID-19.
The Emperor Has No Ganey
Authors: Bonnie L. Bermas
Journal: Annals of Internal Medicine (2022)

LettersJune 2022The Emperor Has No GaneyBonnie L. Bermas, MDBonnie L. Bermas, MDDivision of Rheumatic Diseases, University of Texas Southwestern Medical Center, Dallas, TexasSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L22-0186 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE: Dr. Lee and I agree that the patient experience is an important dimension of quality of care. We also agree that giving providers feedback about patients' perspectives on their clinical experience, whether positive or negative, is invaluable to providers' mission to be at their best and improve health care delivery.I intended for my commentary to start a conversation as to whether patient satisfaction surveys in their current form are the best way to assess the patient experience and give providers constructive areas for improvement in a nonthreatening manner. As they stand now, these surveys are limited by ... Author, Article, and Disclosure InformationAffiliations: Division of Rheumatic Diseases, University of Texas Southwestern Medical Center, Dallas, TexasDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-4075. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Emperor Has No Ganey Bonnie L. Bermas The Emperor Has No Ganey Thomas H. Lee Metrics June 2022Volume 175, Issue 6Page: W64KeywordsHealth care qualityPatient satisfactionPerceptionPsychological stressQuestionnairesRacial and ethnic issuesSub-specialty care ePublished: 21 June 2022 Issue Published: June 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Update on Dry Eye Disease
Authors: David Wirta
Journal: JAMA (2022)

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